Oral esketamine in patients with treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with open-label extension.

About one-third of patients with depression do not achieve adequate response to current treatment options. Although intravenous and intranasal administrations of (es)ketamine have shown antidepressant properties, their accessibility and scalability are limited. We investigated the efficacy, safety, and tolerability of generic oral esketamine in patients with treatment-resistant depression (TRD) in a randomized placebo-controlled trial with open-label extension. This study consisted of 1) a six-week fixed low-dose treatment phase during which 111 participants received oral esketamine 30 mg or placebo three times a day; 2) a four-week wash-out phase; and 3) an optional six-week open-label individually titrated treatment phase during which participants received 0.5 to 3.0 mg/kg oral esketamine two times a week. The primary outcome measure was change in depressive symptom severity, assessed with the Hamilton Depression Rating Scale (HDRS17), from baseline to 6 weeks. Fixed low-dose oral esketamine when compared to placebo had no benefit on the HDRS17 total score (p = 0.626). Except for dizziness and sleep hallucinations scores, which were higher in the esketamine arm, we found no significant difference in safety and tolerability aspects. During the open-label individually titrated treatment phase, the mean HDRS17 score decreased from 21.0 (SD 5.09) to 15.1 (SD 7.27) (mean difference -6.0, 95% CI -7.71 to -4.29, p < 0.001). Our results suggest that fixed low-dose esketamine is not effective in TRD. In contrast, individually titrated higher doses of oral esketamine might have antidepressant properties.

A blended module (STAIRS) to promote functional and personal recovery in patients with a major depressive disorder in remission: study protocol of a concurrent mixed methods randomized controlled trial.

BACKGROUND: Despite the availability of a wide variety of evidence-based treatments for major depressive disorder (MDD), many patients still experience impairments in their lives after remission. Programs are needed that effectively support patients in coping with these impairments. The program Storytelling and Training to Advance Individual Recovery Skills (STAIRS) was developed to address this need and combines the use of peer contact, expert-by-experience guidance, family support and professional blended care. The aim of the planned study is (1) to assess the efficacy of the STAIRS program in patients with remitted MDD, (2) to investigate patients' subjective experiences with STAIRS, and (3) to evaluate the program's cost-effectiveness. METHODS: A concurrent mixed-methods randomized controlled trial design will be used. Patients aged between 18 and 65 years with remitted MDD (N = 140) will be randomized to either a group receiving care as usual (CAU) + the STAIRS-program or a control group receiving CAU + some basic psychoeducation. Quantitative efficacy data on functional and personal recovery and associated aspects will be collected using self-report questionnaires at the start of the intervention, immediately following the intervention, and at the six-month follow-up. Insights into patients' experiences on perceived effects and the way in which different program elements contribute to this effect, as well as the usability and acceptability of the program, will be gained by conducting qualitative interviews with patients from the experimental group, who are selected using maximum variation sampling. Finally, data on healthcare resource use, productivity loss and quality of life will be collected and analysed to assess the cost-effectiveness and cost-utility of the STAIRS-program. DISCUSSION: Well-designed recovery-oriented programs for patients suffering from MDD are scarce. If efficacy and cost-effectiveness are demonstrated with this study and patients experience the STAIRS program as usable and acceptable, this program can be a valuable addition to CAU. The qualitative interviews may give insights into what works for whom, which can be used to promote implementation. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on 1 July 2021, registration number NCT05440812.

Impact of personality functioning and pathological traits on mental wellbeing of older patients with personality disorders.

BACKGROUND: Although personality disorders are common and consequential, they are largely ignored in geriatric mental healthcare. We examined the relative contributions of different aspects of personality disorders and comorbid mental disorders to the impairment of mental wellbeing in older adults. METHODS: Baseline data were used of 138 patients who participated in a randomized controlled trial on schema therapy for geriatric mental health outpatients with a full or subthreshold cluster B or C personality disorder. Personality was assessed according to both the categorical and dimensional model of DSM-5. Aspects of mental wellbeing assessed were; psychological distress, positive mental health, subjective health, and life satisfaction. The current study uses baseline data of the RCT to examine the associations between different aspects of personality pathology and mental wellbeing by multivariate regression analysis, controlling for age, sex, level of education, and number of chronic somatic illnesses. RESULTS: The vast majority of patients (79.0%) had one or more mental disorders in addition to personality disorder. Personality pathology was responsible for the core of the mental health burden experienced by patients, and negated the influence of co-occurring mental disorders when entered subsequently in multivariate analysis. Personality dimensions proved to be highly predictive of mental wellbeing, and this contrasted with absence of influence of personality disorder diagnosis. Although the personality functioning dimensions - and in particular Identity integration (large effect size with partial eta-squared = 0.36) - were the primary predictors of mental wellbeing, personality trait dimensions added significant predictive value to that (Disinhibition 0.25 and Negative affect 0.24). CONCLUSIONS: Personality disorders seriously affect the mental wellbeing of patients, and this overshadows the impact of comorbid mental disorders. In particular personality functioning and pathological traits of the Alternative Model of Personality Disorders (AMPD) of DSM-5 contribute to this impact on mental wellbeing. Alertness for and treatment of personality disorders in geriatric mental healthcare seems warranted.

Study on intracranial meningioma using PET ligand investigation during follow-up over years (SIMPLIFY).

PURPOSE: Radiologic follow-up of patients with a meningioma at the skull base or near the venous sinuses with magnetic resonance imaging (MRI) after stereotactic radiotherapy (SRT) and neurosurgical resection(s) can be difficult to interpret. This study evaluates the addition of 11C-methionine positron emission tomography (MET-PET) to the regular MRI follow-up. METHODS: This prospective pilot study included patients with predominantly WHO grade I meningiomas at the skull base or near large vascular structures. Previous SRT was part of their oncological treatment. A MET-PET in adjunct to their regular MRI follow-up was performed. The standardized uptake value (SUV) was determined for the tumor and the healthy brain, on the pre-SRT target delineation MET-PET and the follow-up MET-PET. Tumor-to-normal ratios were calculated, and 11C-methionine uptake over time was analyzed. Agreement between the combined MRI/MET-PET report and the MRI-only report was determined using Cohen's κ. RESULTS: Twenty patients with stable disease underwent an additional MET-PET, with a median follow-up of 84 months after SRT. Post-SRT SUV T/N ratios ranged between 2.16 and 3.17. When comparing the pre-SRT and the post-SRT MET-PET, five categories of SUV T/N ratios did not change significantly. Only the SUVpeak T/Ncortex decreased significantly from 2.57 (SD 1.02) to 2.20 (SD 0.87) [p = 0.004]. A κ of 0.77 was found, when comparing the MRI/MET-PET report to the MRI-only report, indicating no major change in interpretation of follow-up data. CONCLUSION: In this pilot study, 11C-methionine uptake remained remarkably high in meningiomas with long-term follow-up after SRT. Adding MET-PET to the regular MRI follow-up had no impact on the interpretation of follow-up imaging.

Knowledge and Acceptance Towards Mammography as Breast Cancer Screening Tool Among Yogyakarta Women and Health Care Providers (Mammography Screening in Indonesia).

Annual mammography remains the gold standard of asymptomatic breast cancer screening for women starting at the age of 40. However, Indonesia has not designated mammography as its national screening program. To help policymakers decide whether mammography should be introduced into a national program, it is important to comprehensively understand the knowledge and acceptance of both consumers and providers. A total of 25 subjects including a range of women and health care professionals (HCPs) in Yogyakarta Province were recruited using purposive, maximum variation sampling and then interviewed in-depth. The interviews were recorded and all data were taken and transcribed from the audio recording, which were subsequently translated to English and analyzed thematically. Almost all of Yogyakarta women had heard about the term of mammography. However, only few of them have let themselves be screened, mainly because of their perceived lack of urgency to screen for asymptomatic breast cancer. Another important reason was the high cost of mammography. Meanwhile, several HCPs believed that breast cancer has not been a priority for the government and hence the government limited mammography screening's access and excluded it from the national insurance coverage. Most women in Yogyakarta have a good understanding about breast cancer screening, but their acceptance of mammography as a breast cancer screening tool is significantly influenced by high cost, limited access, and lack of urgency.

Correction to: Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial.

After publication of our article [1] we were notified that Figure 1 was wrongly presented.

Patient-Centered Item Selection for a New Preference-Based Generic Health Status Instrument: CS-Base.

OBJECTIVES: To develop patient-centered health content for a novel generic instrument (Château Santé Base [CS-Base]) that is suitable to generate values for health status. METHODS: Candidate items were drawn from existing health frameworks of generic health status instruments and placed in a diagram (HealthFANTM, Zeist, the Netherlands). Through an online survey, patients with a wide range of diseases were asked to select the 9 items that were most important to them. The importance of the items for the whole study group was determined by means of frequency distributions. RESULTS: After handling duplicates and overlap, the remaining set of 47 items was placed in the HealthFAN. Among the 2256 Dutch patients who started the survey, the most common diagnoses were neck and back pain, diabetes, and asthma/chronic obstructive pulmonary disease. The 5 health items mentioned most frequently as most important were pain, personal relationships, fatigue, memory, and vision. Hearing and vision, anxiety and depression, and independence and self-esteem seemed highly intertwined, so we chose to pair these items. CONCLUSIONS: A total of 12 health items were included in CS-Base. Its content is largely based on patient input and enables classification of patients' health status. CS-Base can be administered by means of an app on a mobile phone, which makes it a convenient and attractive tool for patients and researchers.

Valuing Health Status in the First Year of Life: The Infant Health-Related Quality of Life Instrument.

OBJECTIVES: Efforts to evaluate HRQoL and calculate quality-adjusted life years (QALYs) for infants less than 12 months of age are hampered by the lack of preference-based HRQoL instruments for this group. To fill this gap, we developed the Infant Quality of life Instrument (IQI), which is administered through a mobile application. This article explains how weights were derived for the 4 levels of each health item. METHODS: The IQI includes 7 health items: sleeping, feeding, breathing, stooling/poo, mood, skin, and interaction. In an online survey, respondents from the general population (n = 1409) and primary caregivers (n = 1229) from China, the United Kingdom, and the United States were presented with 10 discrete choice scenarios. Coefficients for the item levels were obtained with a conditional logit model. RESULTS: The highest coefficients were found for sleeping, feeding, and breathing. All coefficients for these items were negative and logically ordered, meaning that more extreme levels were less preferred. Stooling, mood, skin, and interaction showed some irregularities in the ordering of coefficients. Results for caregivers and the general population were about the same. CONCLUSIONS: The IQI is the first generic instrument to assess overall HRQoL in infants up to 1 year of age. It is short and easy to administer through a mobile application. We demonstrated how to derive values for infant health states with a discrete choice methodology. Our next step will be to normalize these values into utilities ranging from 0 (dead) to 1 (best health state) and to collect IQI values in a clinical population.

Health-related quality of life in Indonesian type 2 diabetes mellitus outpatients measured with the Bahasa version of EQ-5D.

OBJECTIVES: To present EuroQol-5D (EQ-5D) index scores in Indonesian type 2 diabetes mellitus (T2DM) outpatients and to investigate the associations between EQ-5D and socio-demographic characteristics and clinical condition. METHODS: Socio-demographic data were collected by interviewing participants, clinical data were obtained from treating physicians and self-reporting. Participants originated from primary and secondary care facilities in the Java and Sulawesi regions. Ordinal regression analysis was conducted with the quintiles of the EQ-5D index scores as the dependent variable to investigate the multivariate association with the participants' socio-demographic characteristics and clinical condition. RESULTS: 907 participants completed the five-level Indonesian version of the EQ-5D. The mean age of the participants was 59.3 (SD 9.7), and 57% were female. The overall EQ-5D index score was 0.77 (0.75-0.79). Male participants had a higher EQ-5D index score compared to females, and the highest percentage of self-reported health problems was in the pain/discomfort dimension (61%). Factors identified as being significantly associated with lower EQ-5D index scores were: (i) treatment in secondary care, (ii) lower educational level, (iii) dependency on caregivers, (iv) not undergoing T2DM therapy, and (v) being a housewife. CONCLUSION: This study provides estimates of EQ-5D index scores that can be used in health economic evaluations. As housewives were found to experience more T2DM-related pain/discomfort and anxiety/depression, targeted approaches to reduce these problems should be aimed specifically at this group of patients. Potential approaches could involve disease-specific-counselors (health literacy partners) who provide routine monitoring of T2DM therapy as well as improved health promotion among T2DM communities.

Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial.

BACKGROUND: There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. METHODS: This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. DISCUSSION: This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. TRIAL REGISTRATION: Dutch Trial Register, NTR6161. Registered 21 October 2016.

Diabetes distress in Indonesian patients with type 2 diabetes: a comparison between primary and tertiary care.

BACKGROUND: The number of people living with diabetes mellitus (DM) in Indonesia has continued to increase over the last 6 years. Four previous studies in U.S have found that higher DD scores were associated with worse psychological outcomes, lower health-related quality of life (HRQoL) and increased risk of T2DM complications. In this study, we aimed to firstly compare DD scores in Indonesian T2DM outpatients treated in primary care versus those in tertiary care. Subsequently, we investigated whether socio-demographic characteristics and clinical conditions explain potential differences in DD score across healthcare settings. METHODS: A cross-sectional study was conducted on Java island in three primary care (n = 108) and four tertiary care (n = 524) facilities. The participants completed the Bahasa Indonesia version of the Diabetes Distress Scale questionnaire (DDS17 Bahasa Indonesia). Ordinal regression analysis was conducted with the quartile of the summation of the DD score as the dependent variable to investigate how the association between the level of healthcare facilities and DD altered when adding different variables in the model. RESULTS: The final adjusted model showed that the level of healthcare facilities was strongly associated with DD (p < .001), with participants in primary care having a 3.68 times (95% CI 2.46-5.55) higher likelihood of being more distressed than the participants in tertiary care. This association was detected after including the socio-demographic characteristics and clinical conditions as model confounders. CONCLUSIONS: This is the first study in Indonesia to compare DD scores within different healthcare facilities. We recommend a regular DD assessment, possibly closely aligned with health-literacy partner programs, especially for T2DM patients in primary care settings.

Identifying and prioritizing lower value services from Dutch specialist guidelines and a comparison with the UK do-not-do list.

BACKGROUND: The term 'lower value services' concerns healthcare that is of little or no value to the patient and consequently should not be provided routinely, or not be provided at all. De-adoption of lower value care may occur through explicit recommendations in clinical guidelines. The present study aimed to generate a comprehensive list of lower value services for the Netherlands that assesses the type of care and associated medical conditions. The list was compared with the NICE do-not-do list (United Kingdom). Finally, the feasibility of prioritizing the list was studied to identify conditions where de-adoption is warranted. METHODS: Dutch clinical guidelines (published from 2010 to 2015) were searched for lower value services. The lower value services identified were categorized by type of care (diagnostics, treatment with and without medication), type of lower value service (not routinely provided or not provided at all), and ICD10 codes (international classification of diseases). The list was prioritized per ICD10 code, based on the number of lower value services per ICD10 code, prevalence, and burden of disease. RESULTS: A total of 1366 lower value services were found in the 193 Dutch guidelines included in our study. Of the lower value services, 30% covered diagnostics, 29% related to surgical and medical treatment without drugs primarily, and 39% related to drug treatment. The majority (77%) of all lower value services was on care that should not be offered at all, whereas the other 23% recommended on care that should not be offered routinely. ICD10 chapters that included most lower value services were neoplasms and diseases of the nervous system. Dutch guidelines appear to contain more lower value services than UK guidelines. The prioritization processes revealed several conditions, including back pain, chronic obstructive pulmonary disease, and ischemic heart diseases, where lower value services most likely occur and de-adoption is warranted. CONCLUSIONS: In this study, a comprehensive list of lower value services for Dutch hospital care was developed. A feasible method for prioritizing lower value services was established. Identifying and prioritizing lower value services is the first of several necessary steps in reducing them.

An Online Health Prevention Intervention for Youth with Addicted or Mentally Ill Parents: Experiences and Perspectives of Participants and Providers from a Randomized Controlled Trial.

BACKGROUND: Mental illnesses affect many people around the world, either directly or indirectly. Families of persons suffering from mental illness or addiction suffer too, especially their children. In the Netherlands, 864,000 parents meet the diagnostic criteria for a mental illness or addiction. Evidence shows that offspring of mentally ill or addicted parents are at risk for developing mental disorders or illnesses themselves. The Kopstoring course is an online 8-week group course with supervision by 2 trained psychologists or social workers, aimed to prevent behavioral and psychological problems for children (aged 16 to 25 years) of parents with mental health problems or addictions. The course addresses themes such as roles in the family and mastery skills. An online randomized controlled trial (RCT) was conducted to assess the effectiveness of the Kopstoring course. OBJECTIVE: The aim was to gain knowledge about expectations, experiences, and perspectives of participants and providers of the online Kopstoring course. METHODS: A process evaluation was performed to evaluate the online delivery of Kopstoring and the experiences and perspectives of participants and providers of Kopstoring. Interviews were performed with members from both groups. Participants were drawn from a sample from the Kopstoring RCT. RESULTS: Thirteen participants and 4 providers were interviewed. Five main themes emerged from these interviews: background, the requirements for the intervention, experience with the intervention, technical aspects, and research aspects. Overall, participants and providers found the intervention to be valuable because it was online; therefore, protecting their anonymity was considered a key component. Most barriers existed in the technical sphere. Additional barriers existed with conducting the RCT, namely gathering informed consent and gathering parental consent in the case of minors. CONCLUSIONS: This study provides valuable insight into participants' and providers' experiences and expectations with the online preventive intervention Kopstoring. It also sheds light on the process of the online provision of Kopstoring and the accompanying RCT. The findings of this study may partly explain dropout rates when delivering online interventions. The change in the (financial) structure of the youth mental health care system in the Netherlands has financial implications for the delivery of prevention programs for youth. Lastly, there are few RCTs that assess the effectiveness and cost-effectiveness of online prevention programs in the field of (youth) mental health care and not many process evaluations of these programs exist. This hampers a good comparison between online interventions and the expectations and experiences of the participants and providers. TRIAL REGISTRATION: Nederlands Trial Register: NTR1982; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1982 (Archived by WebCite® at http://www.webcitation.org/6d8xYDQbB).

Lessons Learned from Model-based Economic Evaluations of COVID-19 Drug Treatments Under Pandemic Circumstances: Results from a Systematic Review.

BACKGROUND: Following clinical research of potential coronavirus disease 2019 (COVID-19) treatments, numerous decision-analytic models have been developed. Due to pandemic circumstances, clinical evidence was limited and modelling choices were made under great uncertainty. This study aimed to analyse key methodological characteristics of model-based economic evaluations of COVID-19 drug treatments, and specifically focused on modelling choices which pertain to disease severity levels during hospitalisation, model structure, sources of effectiveness and quality of life and long-term sequelae. METHODS: We conducted a systematic literature review and searched key databases (including MEDLINE, EMBASE, Web of Science, Scopus) for original articles on model-based full economic evaluations of COVID-19 drug treatments. Studies focussing on vaccines, diagnostic techniques and non-pharmaceutical interventions were excluded. The search was last rerun on 22 July 2023. Results were narratively synthesised in tabular form. Several aspects were categorised into rubrics to enable comparison across studies. RESULTS: Of the 1047 records identified, 27 were included, and 23 studies (85.2%) differentiated patients by disease severity in the hospitalisation phase. Patients were differentiated by type of respiratory support, level of care management, a combination of both or symptoms. A Markov model was applied in 16 studies (59.3%), whether or not preceded by a decision tree or an epidemiological model. Most cost-utility analyses lacked the incorporation of COVID-19-specific health utility values. Of ten studies with a lifetime horizon, seven adjusted general population estimates to account for long-term sequelae (i.e. mortality, quality of life and costs), lasting for 1 year, 5 years, or a patient's lifetime. The most often reported parameter influencing the outcome of the analysis was related to treatment effectiveness. CONCLUSION: The results illustrate the variety in modelling approaches of COVID-19 drug treatments and address the need for a more standardized approach in model-based economic evaluations of infectious diseases such as COVID-19. TRIAL REGISTRY: Protocol registered in PROSPERO under CRD42023407646.

The value of artificial intelligence for the treatment of mechanically ventilated intensive care unit patients: An early health technology assessment.

PURPOSE: The health and economic consequences of artificial intelligence (AI) systems for mechanically ventilated intensive care unit patients often remain unstudied. Early health technology assessments (HTA) can examine the potential impact of AI systems by using available data and simulations. Therefore, we developed a generic health-economic model suitable for early HTA of AI systems for mechanically ventilated patients. MATERIALS AND METHODS: Our generic health-economic model simulates mechanically ventilated patients from their hospitalisation until their death. The model simulates two scenarios, care as usual and care with the AI system, and compares these scenarios to estimate their cost-effectiveness. RESULTS: The generic health-economic model we developed is suitable for estimating the cost-effectiveness of various AI systems. By varying input parameters and assumptions, the model can examine the cost-effectiveness of AI systems across a wide range of different clinical settings. CONCLUSIONS: Using the proposed generic health-economic model, investors and innovators can easily assess whether implementing a certain AI system is likely to be cost-effective before an exact clinical impact is determined. The results of the early HTA can aid investors and innovators in deployment of AI systems by supporting development decisions, informing value-based pricing, clinical trial design, and selection of target patient groups.

Mechanical ventilation as a major driver of COVID-19 hospitalization costs: a costing study in a German setting.

BACKGROUND: While COVID-19 hospitalization costs are essential for policymakers to make informed health care resource decisions, little is known about these costs in western Europe. The aim of the current study is to analyze these costs for a German setting, track the development of these costs over time and analyze the daily costs. METHODS: Administrative costing data was analyzed for 598 non-Intensive Care Unit (ICU) patients and 510 ICU patients diagnosed with COVID-19 at the Frankfurt University hospital. Descriptive statistics of total per patient hospitalization costs were obtained and assessed over time. Propensity scores were estimated for length of stay (LOS) at the general ward and mechanical ventilation (MV) duration, using covariate balancing propensity score for continuous treatment. Costs for each additional day in the general ward and each additional day in the ICU with and without MV were estimated by regressing the total hospitalization costs on the LOS and the presence or absence of several treatments using generalized linear models, while controlling for patient characteristics, comorbidities, and complications. RESULTS: Median total per patient hospitalization costs were €3,010 (Q1 - Q3: €2,224-€5,273), €5,887 (Q1 - Q3: €3,054-€10,879) and €21,536 (Q1 - Q3: €7,504-€43,480), respectively, for non-ICU patients, non-MV and MV ICU patients. Total per patient hospitalization costs for non-ICU patients showed a slight increase over time, while total per patient hospitalization costs for ICU patients decreased over time. Each additional day in the general ward for non-ICU COVID-19 patients costed €463.66 (SE: 15.89). Costs for each additional day in the general ward and ICU without and with mechanical ventilation for ICU patients were estimated at €414.20 (SE: 22.17), €927.45 (SE: 45.52) and €2,224.84 (SE: 70.24). CONCLUSIONS: This is, to our knowledge, the first study examining the costs of COVID-19 hospitalizations in Germany. Estimated costs were overall in agreement with costs found in literature for non-COVID-19 patients, except for higher estimated costs for mechanical ventilation. These estimated costs can potentially improve the precision of COVID-19 cost effectiveness studies in Germany and will thereby allow health care policymakers to provide better informed health care resource decisions in the future.

Cost-Effectiveness of Test-and-Treat Strategies to Reduce the Antibiotic Prescription Rate for Acute Febrile Illness in Primary Healthcare Clinics in Africa.

BACKGROUND: Inappropriate antibiotic use increases selective pressure, contributing to antimicrobial resistance. Point-of-care rapid diagnostic tests (RDTs) would be instrumental to better target antibiotic prescriptions, but widespread implementation of diagnostics for improved management of febrile illnesses is limited. OBJECTIVE: Our study aims to contribute to evidence-based guidance to inform policymakers on investment decisions regarding interventions that foster more appropriate antibiotic prescriptions, as well as to address the evidence gap on the potential clinical and economic impact of RDTs on antibiotic prescription. METHODS: A country-based cost-effectiveness model was developed for Burkina Faso, Ghana and Uganda. The decision tree model simulated seven test strategies for patients with febrile illness to assess the effect of different RDT combinations on antibiotic prescription rate (APR), costs and clinical outcomes. The incremental cost-effectiveness ratio (ICER) was expressed as the incremental cost per percentage point (ppt) reduction in APR. RESULTS: For Burkina Faso and Uganda, testing all patients with a malaria RDT was dominant compared to standard-of-care (SoC) (which included malaria testing). Expanding the test panel with a C-reactive protein (CRP) test resulted in an ICER of $ 0.03 and $ 0.08 per ppt reduction in APR for Burkina Faso and Uganda, respectively. For Ghana, the pairwise comparison with SoC-including malaria and complete blood count testing-indicates that both testing with malaria RDT only and malaria RDT + CRP are dominant. CONCLUSION: The use of RDTs for patients with febrile illness could effectively reduce APR at minimal additional costs, provided diagnostic algorithms are adhered to. Complementing SoC with CRP testing may increase clinicians' confidence in prescribing decisions and is a favourable strategy.

The role of cardiovascular magnetic resonance imaging and computed tomography angiography in suspected non-ST-elevation myocardial infarction patients: design and rationale of the CARdiovascular Magnetic rEsoNance imaging and computed Tomography Angiography (CARMENTA) trial.

BACKGROUND: Although high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non-ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA. STUDY DESIGN: In this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness. CONCLUSION: The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome.

Early Detection of Breast Cancer in Indonesia: Barriers Identified in a Qualitative Study.

BACKGROUND: The lack of early detection in breast cancer management has been identified as the primary factor contributing to the high mortality rate. The introduction of BPJS Kesehatan, Indonesia's national health insurance, was intended to ensure the provision of adequate health services for breast cancer patients. This study aimed to investigate the current state of health services in Indonesia concerning the early detection of breast cancer, following the implementation of BPJS Kesehatan introduction. METHODS: The study was conducted in 2017 in Yogyakarta, Indonesia. Subjects were recruited using a purposive sampling technique with maximum variation. The sample comprised breast cancer patients, health care professionals (HCPs), and healthy women from the general population with no history of breast cancer. The subjects' experiences and knowledge of health services regarding the early detection of breast cancer were investigated through in-depth interviews. Thematic analysis was used to synthesize the results from interviews with 25 participants. RESULT: This study identified several issues that hinder the timely detection of breast cancer. The lack of both screening and diagnostic procedures emerged as a prominent obstacle in breast cancer management. The study identified the following barriers: (1) limited community knowledge about early detection; (2). lack of urgency among patients to seek medical treatment; (3) limited access to health facilities; and (4) inconsistent adherence among health care professionals to guidelines for both screening and diagnostic procedures. CONCLUSIONS: This study revealed multiple factors contributing to the delay in breast cancer detection in Indonesia, leading to suboptimal management of the disease. It is crucial for the government to prioritize the improvement of enabling factors across all levels of care for early detection. These factors include initiatives to increase public awareness, improve access to health services, strengthen the referral system, and enhance health facilities.

Cost-effectiveness analysis of a first-trimester screening test for preterm preeclampsia in the Netherlands.

OBJECTIVES: The risk of preterm preeclampsia (PT PE) can significantly be reduced by starting acetylsalicylic acid ≤ 16 weeks of gestational age. First trimester predictive models based on maternal risk factors to effectively start this therapy lacked sufficient power, but recent studies showed that these models can be improved by including test results of biochemical and/or -physical markers. To investigate whether testing a biochemical marker in the first trimester is cost-effective in the Netherlands, a cost-effectiveness analysis was performed in this study. STUDY DESIGN: The outcome of this study was expressed as an incremental cost-effectiveness ratio (ICER) with as effect prevented PT PE cases. To evaluate the impact of each model parameter and to determine model uncertainties, both univariate and probabilistic sensitivity analyses were performed. RESULTS: When compared to the baseline strategy, the test strategy is estimated to save almost 4 million euros per year on a national scale and at the same time this would prevent an additional 228 PT PE cases. The sensitivity analyses showed that the major drivers of the result are the costs to monitor a high-risk pregnancy and the specificity and that most of the model simulations were in the southeast quadrant: cost saving and more prevented complications. CONCLUSIONS: This study showed that a first-trimester test strategy to screen for PT PE in the first trimester is potentially cost-effective in the Dutch healthcare setting. The fact that the specificity is a major driver of the ICER indicates the importance for a (new) screening model to correctly classify low-risk pregnancies.